Many older patients at risk for infections are receiving home healthcare (HHC) services. In a systematic review we found little is known about infections occurring while patients are enrolled in HHC and how best to mitigate infection risk for these vulnerable patients. In pilot work (R03 NR013966), using 2010 national Outcome and Assessment Information Set (OASIS) data, we have found infections to be a common reason for unplanned hospitalizations among HHC patients. However, OASIS data are limited and likely underestimate the true infection rate. We also found agency-level infection rates varied greatly across the country. The variation across agencies may indicate that recommended guidelines are not being adopted and/or that there are limitations in the guidelines themselves. The HHC environment is the fastest growing healthcare sector in the nation but is less controlled than other settings, is increasing in complexity with patients being discharged from hospitals earlier, and care is often provided by patients, family members, or personal aides with little or no formal training in infection prevention. Informed by our systematic review, pilot work, and Andersen's Behavioral Model for Vulnerable Populations, we propose a 4-year, multiple methods study with the following aims: 1) describe the incidence of infections that occur while patients are receiving HHC and the relationship with patients' predisposing, enabling, and need characteristics; 2) describe the current infection prevention and control infrastructure and policies in HHC agencies; 3) compare the effectiveness of various infection prevention and control infrastructures and policies in preventing infections in HHC; and 4) estimate survival and healthcare utilization associated with infections in HHC patients. In Aim 1, we will use the most current (2013-2015) administrative data (e.g., OASIS and Medicare claims) from 3,333 randomly sampled agencies. In Aim 2, qualitative in-depth, open-ended interviews will be conducted in 12 HHC agencies across the nation to inform the phenomena of infection prevention, refinement of our survey, and Aims 3 and 4. Then, we will survey HHC agencies (expected sample n = 1,333). For Aim 3, we will link the survey data with concurrent patient (n = 133,300) and agency (n = 1,333) data. For Aim 4, we will use longitudinal data (2013-2017) on up to 1 million patients. The econometric analyses will address patients nested within HHC agencies, assess individual risk, and minimize threats to validity. Our multidisciplinary research team is ideally qualified to conduct this study, which will be the first of its kind in HHC. Focusing on infection prevention and control efforts in HHC across the nation is innovative and will extend the infection prevention research paradigm. Results will be seminal in the HHC setting, and evidence developed from this project will inform authors of future practice guidelines, clinicians, managers, and policy makers on the problem of infections and how best to mitigate risk. This research is consistent with NINR's strategic mission that emphasizes multidisciplinary research that develops knowledge to improve wellness and prevent disease.